What is the recommended dosing for bupropion (Wellbutrin) XL in a patient with major depressive disorder or seasonal affective disorder, considering potential seizure risk and impaired renal or hepatic function?

Bupropion XL Dosing for Major Depressive Disorder and Seasonal Affective Disorder

For major depressive disorder, start bupropion XL at 150 mg once daily in the morning, then increase to the target dose of 300 mg once daily after 4 days. 1 For seasonal affective disorder, use the same 150 mg starting dose but wait 7 days before increasing to 300 mg once daily. 1

Standard Dosing Protocol

Major Depressive Disorder

• Initial dose: 150 mg once daily in the morning 1
• Titration: Increase to 300 mg once daily after 4 days of treatment 1
• Target dose: 300 mg once daily 1
• Administration: Take in the morning, with or without food; swallow whole without crushing, dividing, or chewing 1

Seasonal Affective Disorder

• Initial dose: 150 mg once daily 1
• Titration: Increase to 300 mg once daily after 7 days 1
• Target dose: 300 mg once daily 1
• Timing: Initiate in autumn before depressive symptoms begin, continue through winter, then taper in early spring 1, 2
• Prevention efficacy: Starting treatment while patients are still well reduces depression recurrence by 44% compared to placebo 2

Critical Seizure Risk Management

The maximum daily dose must never exceed 450 mg to minimize seizure risk, which is approximately 1 in 1,000 at therapeutic doses. 3, 1 The gradual dose titration is mandatory to reduce this risk. 1

Absolute Contraindications

• Current or prior seizure disorder 1
• Current or prior diagnosis of bulimia or anorexia nervosa 1
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
• Concurrent MAOI use or within 14 days of MAOI discontinuation 1

Conditions Requiring Extreme Caution

• History of head trauma, brain tumor, or stroke 3
• Uncontrolled hypertension 3
• Concurrent medications that lower seizure threshold 3

Dose Adjustments for Organ Impairment

Hepatic Impairment

• Moderate to severe (Child-Pugh 7-15): Maximum dose is 150 mg every other day 1, 3
• Mild (Child-Pugh 5-6): Reduce dose and/or frequency; specific reduction not defined but consider 150 mg daily 1, 3

Renal Impairment

• GFR <90 mL/min: Reduce dose and/or frequency by approximately 50% 1, 3
• End-stage renal disease: Avoid use 4, 3
• Rationale: Bupropion and its active metabolites are cleared renally and may accumulate 3

Monitoring Requirements

Initial Assessment

• Screen for seizure risk factors, eating disorders, and bipolar disorder 3, 1
• Measure baseline blood pressure, as bupropion can elevate blood pressure and heart rate 3
• Assess for suicidal ideation, particularly in patients under 24 years old 3, 1

Ongoing Monitoring

• First 1-2 weeks: Monitor closely for worsening depression, suicidal thoughts, or behavioral changes—the highest risk period for suicide attempts 3, 1
• First 12 weeks: Check blood pressure and heart rate periodically 3
• 6-8 weeks: Assess therapeutic response; if inadequate, consider treatment modification 3
• Throughout treatment: Watch for neuropsychiatric symptoms including agitation, anxiety, psychosis, or mania 3, 1

Discontinuation Protocol

When discontinuing bupropion XL 300 mg daily, taper to 150 mg once daily before complete discontinuation. 1 For seasonal affective disorder, taper in early spring when seasonal risk has passed. 1

• Maintain treatment for at least 4 months for a first depressive episode before considering discontinuation 5
• Monitor closely during tapering, as suicide risk may persist 5
• The evidence does not provide explicit tapering schedules beyond the single-step reduction from 300 mg to 150 mg 5

Special Clinical Considerations

Drug Interactions

• MAOIs: Allow 14 days between stopping an MAOI and starting bupropion, or vice versa 1
• Reversible MAOIs (linezolid, IV methylene blue): Do not initiate bupropion in patients receiving these agents due to hypertensive crisis risk 1
• CYP2D6 substrates: Bupropion inhibits CYP2D6, potentially increasing levels of drugs metabolized by this pathway 6

Formulation Switching

• When switching from immediate-release or SR formulations to XL, use the same total daily dose when possible 1
• Critical pitfall: Monitor closely when switching between brand and generic formulations due to historical bioequivalence issues that may cause loss of antidepressant effect 3, 5

Advantages Over Other Antidepressants

• Significantly lower rates of sexual dysfunction compared to SSRIs 3, 6
• Associated with minimal weight gain or even weight loss 3
• Lower rates of sedation than SSRIs 3
• May be particularly beneficial for patients with depression characterized by low energy, apathy, or hypersomnia due to activating properties 3

Common Adverse Effects

• Dry mouth, nausea, insomnia, dizziness, agitation, anxiety, tremor 1, 6
• Delayed hypersensitivity reactions (pruritus, urticaria) can occur 2+ weeks after initiation, particularly in males aged 17-40 years 7

Duration of Treatment

• Acute episodes of depression require several months or longer of treatment beyond initial response 1
• Periodically reassess the need for maintenance treatment and appropriate dosing 1
• For seasonal affective disorder, treatment duration is individualized based on the patient's historical pattern of seasonal episodes 1